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There are increasing numbers of HIV-infected patients in sub-Saharan Africa receiving antiretroviral drugs and/or rifampicin based antituberculous therapy. HIV infected patients are at an increased risk of contracting malaria. Increasing resistance to anti-malarials such as chloroquine, amodiaquine, fansidar, sulphadoxine-pyrimethamine in East and West Africa has led the WHO to recommend artemether-lumefantrine (Coartem®- Novartis) as first line therapy for malaria for adults and children. As early as 2004, fourteen countries in sub-Saharan Africa had adopted this guideline as national policy.

There are no data on the interaction between Coartem® and any of the antiretroviral agents. Both components of Coartem® are substrates for the 3A4 isoform of cytochrome P450. Despite the lack of data, antiretroviral drugs and/or antituberculous drugs in addition to Coartem® are of necessity co-prescribed daily in the African setting. Nevirapine, efavirenz and rifampicin are known inducers of cytochrome P450 3A4. A technical consultation convened by WHO in June, 2004 concluded that additional research on interactions between antiretroviral and antimalarial drugs is urgently needed.

We propose to perform a suite of pharmacokinetic studies to evaluate these interactions in HIV infected Ugandan patients. The aim of these studies is to evaluate the pharmacokinetic interaction between Coartem® and commonly co-prescribed inducers of 3A4 i.e. nevirapine, efavirenz and rifampicin.

Comparison of steady state pharmacokinetics of Coartem® in HIV-infected patients prior to commencement of nevirapine and at nevirapine steady state

Comparison of steady state pharmacokinetics of Coartem® in HIV-infected patients prior to commencement of efavirenz and at efavirenz steady state

Comparison of steady state pharmacokinetics of Coartem® in Ugandan patients at rifampicin steady state and without rifampicin

Administration of lumefantrine 480mg co-formulated with artemether 80mg twice daily for three days to HIV positive patients receiving nevirapine 200mg twice daily as part of their antiretroviral treatment

Other Names:

Coartem

Triomune

Experimental: 2

efavirenz arm

Drug: lumefantrine-artemether and efavirenz

Administration of lumefantrine 480mg co-formulated with artemether 80mg twice daily for three days to HIV positive adults receiving efavirenz tablets 600mg once daily

Other Names:

Coartem

Sustiva

Experimental: 3

Rifampicin arm

Drug: Lumefantrine-artemether and rifampicin

Administration of lumefantrine 480mg co-formulated with artemether 80mg twice daily for three days to patients receiving rifampicin as part of fixed dose combination therapy for tuberculosis

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Ages Eligible for Study:

18 Years to 60 Years (Adult)

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Age over eighteen years

Ability to provide full written informed consent

Confirmed diagnosis of HIV infection

Exclusion Criteria:

Haemoglobin < 8g/dl

Liver and renal function tests > 3 times the upper limit of normal

Pregnancy

Use of known inhibitors or inducers of cytochrome P450 or P-glycoprotein.

Use of herbal medications (information will be obtained from patients' medication history through interview with the patient)